Radiation synovectomy produces functional ablation of inflamed synovium following intra-articular administration of short-range, beta-emitting radioisotopes. The isotope is complexed to a particulate carrier in order to delay and decrease leakage rom the joint, thereby reducing the total body radiation exposure. We have developed a new agent for radiation synovectomy - dysprosium-165-ferric hydroxide macroaggregates (165Dy-FHMA) - and have been using it in clinical trials over the past six years. Ninety-five of 112 (85%) rheumatoid knees showed significant improvement one year after treatment. Leakage of radioactivity from the treated joint has been less than 1% of the injected dose. We propose to conduct a prospective trial of 165Dy-FHMA to confirm the efficacy indicated in our previous uncontrolled studies. Anticipating a favorable outcome from these studies, and recognizing the impractical half life of 165Dy, we propose to develop new agents that will be appropriate for use in areas not adjacent to a reactor, greatly extending the availability of this therapy. Other isotopes and carrier systems, in various combinations, will be investigated in the animal model of antigen-induced arthritis. Potential isotopes include rhenium 188 and yttrium-90; carriers include FHMA, sulfur colloids and lipophilic complexes. In addition to its usefulness in rheumatoid arthritis of the knee (and potentially other joints), our preliminary studies in hemophilic arthropathy of the knee and pigmented villonodular synovitis indicate a high degree of probability that radiation synovectomy will be useful in these disorders as well. Objective evaluation of the efficacy of treatment remains problematic; to address this problem, we propose to continue our investigation of indium-111 scanning as a clinically useful, objective and quantitative indicator of inflammation in the synovial tissues.